THE INFLUENCE OF AGE AND GENDER UPON THE EFFECTS OF CHRONIC NEUROINFLAMMATION





G.L. Wenk*, L. Marriott, B. Hauss-Wegrzyniak

Division of Neural Systems, Memory & Aging, University of Arizona, Tucson, AZ 85724



Chronic neuoinflammation and gender may play an important role in the pathogenesis of Alzheimer’s disease (AD). The present study compared the effects of chronic neuroinflammation, produced by infusion of lipopolysaccharide (LPS) into the 4th ventricle, upon memory and level of inflammation in two different experimental animal models: 1) young, adult and old male rats, and 2) young female rats with and without ovariectomy. Chronic LPS infusions impaired the baseline performance of young male rats, but not adult or old male rats. Treatment with an NO-containing, non-steroidal anti-inflammatory drug (nitro-flurbiprofen, NFP) improved the performance of LPS-infused young male rats, but not LPS-infused adult or old male rats. LPS infusions increased the number of activated microglia in young and adult rats, but not old male rats. NFP treatment attenuated the effects of LPS upon microglia activation in young and adult rats, but not old male rats. Intact females receiving LPS infusion were not impaired in the water maze task and had significantly fewer activated microglia than male rats. The removal of the ovaries did not impair water maze performance; however, addition of chronic ERT or neuroinflammation resulted in an impairment that became exacerbated by the simultaneous occurrence of both conditions. Chronic LPS activated microglia, which was not reduced by estrogen replacement therapy. Our results suggest that 1) anti-inflammatory therapy must begin prior to the onset of inflammation associated with normal aging and 2) that chronic estrogen replacement therapy in post-menopausal women may exacerbate the memory impairment induced by the chronic neuroinflammation associated with AD.




Key words: neuroinflammation, rats, aging, estrogen, LPS







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